Effects of ibogaine on the development of tolerance to antinociceptive action of mu-, delta- and kappa-opioid receptor agonists in mice.

The effects of ibogaine, an alkaloid isolated from the bark of the African shrub, Tabernanthe iboga, on the development of tolerance to the antinociception action of morphine, U-50,488H and [D-Pen2,D-Pen5]enkephalin (DPDPE), which are mu-, kappa- and delta-opioid receptor agonists, respectively, were determined in male Swiss-Webster mice. Mice were rendered tolerant to opioid receptor agonists by injecting morphine (20 mg/kg, s.c.), U-50,488H (25 mg/kg, i.p.) or DPDPE (20 microg/mouse, i.c.v.) twice a day for 4 days. Ibogaine (20, 40 or 80 mg/kg, i.p.) given twice a day for 4 days did not alter the tail-flick latency. Ibogaine (40 or 80 mg/kg, i.p.) injected 10 min before each injection of morphine inhibited the development of tolerance to the antinociceptive action of morphine, however, the lower dose of ibogaine (20 mg/kg, i.p.) was ineffective. Ibogaine (20, 40 or 80 mg/kg, i.p.) given prior to the injection of U-50,488H or DPDPE did not modify the development of tolerance to their antinociceptive action. It is concluded that ibogaine inhibits selectively the development of tolerance to the antinociceptive action of mu- but not kappa- or delta-opioid receptor agonists in mice.